Transport System Smuggles Medicine into Brain

The blood-brain barrier (BBB) between the blood circle and the brain only lets through important nutrients for the brain such as iron, glucose and oxygen. Dr Corine Visser of the Leiden/Amsterdam Center for Drug Research, allowed larger molecules, such as medicines, to pass through the blood-brain barrier by attaching these to the iron-containing protein transferring, as specified in her doctoral thesis.

The technique allowed the medicine to 'hitch a lift' and pass unnoticed through the BBB. Much of the BBB is made up of capillary endothelial cells, closely packed together. This makes it almost impossible for substances to pass between the cells.

According to Visser, the amount of medicine reaching the brain depends on the size of the molecule attached to the transferring. Transferrin contains two iron atoms. On reaching the BBB it binds to transferrin receptors on the endothelial cells. Once the transferrin has bound to the receptor, a vesicle in the cell completely engulfs it. The transferrin then releases the iron atoms, which are brought to the brain by another protein.

Visser investigated the transport in three stages. In the first stage she demonstrated the presence of the receptor in her BBB model by using radioactively-labelled transferrin. She then conjugated an enzyme to the transferrin. With the attached enzyme, the transferrin also bound to the receptor and was taken up in the cells of the BBB.

Finally, Visser attached a liposome containing small molecules, such as medicines, to the transferrin. She discovered that the transferrin with the liposome attached was also taken up by the cell. However, the cell subsequently broke down the liposomal content, because the liposomes were significantly bigger than the previously linked enzyme. Therefore, a liposome or a direct conjugation can be chosen, dependent on the intracellular destination of the medicine.